The ultimate goal of this research is to characterize the forces directing nucleic acid chemistry, and to use this knowledge to reliably predict structures of RNA molecules from their sequences. Since the action of viruses is mediated through RNA, and some viruses, including AIDS, are RNA, the results can lead to rational design of drugs. The foundation for structure prediction will be provided by studies of the thermodynamic, dynamic, and structural properties of oligonucleotides. Our understanding of the general principles governing nucleic acid chemistry will be tested by studies on the structure and mechanism of the self splicing intervening sequence (IVS) from the ribosomal RNA precursor in Tetrahymena thermophila. This is the first RNA known to break and make covalent bonds, and the results will provide important insights into the detailed mechanism of this newly discovered phenomenon.